We propose to study new types of synthetic water soluble polymers for treatment of colon disease based on the concept of binding of polymeric carriers containing carbohydrate moieties complementary to mucosal lectins and on the concept of site- specific release of drugs by the action of bacterial enzymes. The aim is to devise copolymer-drug conjugates which will increase the effectiveness of drugs given orally. Our preliminary studies demonstrated that: 1) By attachment of monosaccharides (glucose, fucose) to N-(2- hydroxypropyl)methacrylamide copolymers it is possible to prolong their transit time in the G.I. tract of experimental animals (rats) and specific binding in the colon. 2) Chemical reactions were developed which are necessary to bind 5-aminosalicylic acid to polymeric carriers via azo bonds and to attach to the same polymeric chain bioadhesive moieties (monosaccarides). In this application, N-(2-hydroxypropyl)methacrylamide copolymers will be synthesized which will contain both, 5- aminosaliciylic acid attached via azo bonds and bioadhesive moieties (galactosamines, glucosamine and fucosylamine), attached via amide bonds. The former will yield by biodegradation in the colon 5-aminosalicylic acid (a potent drug against ulcerative colitis), the latter will be responsible for the specific binding to lectins in the G.I. tract. The polymers will be characterized by physicochemcial methods and the relationship between their structure and properties will be determined will emphasis on: a) The relation between the type of monosaccharide and the bioadhesive properties in vitro and in vivo. b) The relationship between the detailed structure of copolymers and the rate of release and body distribution in vitro and in vivo. Based on these results optimal structures will be chosen and a study of the therapeutic efficacy of polymer bound 5-ASA on an animal model of ulcerative colitis will be undertaken. The results of proposed studies will provide a new therapeutic method for the treatment of chronic colon disease such as ulcerative colitis.